Ana Carolina Migliorini Figueira

My research focuses on metabolism and hormone signaling control, particularly studying biochemical and structural aspects of nuclear receptors (NRs). The regulation of these proteins exists to promote a common control of gene expression in different tissues and developmental stages. These proteins are related to metabolic syndrome, diabetes, cardiopathies, cancer and obesity; acting in transcriptional regulation, generally, modulated by ligand binding. Data compiled show that medical prescriptions targeting nuclear receptors are increasing during the years. Today, these drugs account for over 30 billion dollars in pharmaceutical sales. In this context, the importance of these proteins as drug targets is evident. My current goal is to study the interactions between RNs, proteins, small molecules and DNA regulatory sequences aiming better understanding the mechanisms of action of NRs and their ligand modulation. These studies will be made by biochemical, biophysical and structural biology point of views.

CURRENT PROJECTS

Searching ligands for NRs.

The metabolic syndrome reaches at least 25% of world population, been characterized as a combination of pathologies like hypertension, obesity, diabetes, inflammation, and cardiopathies. Many efforts to combat this disease aim to modulate many nuclear receptors, like PPAR.

In this projects we intend o identify new molecules that can modulate NRs like Thyroid Hormone Receptor (TR) and Peroxissome Proliferator Activated Receptor (PPAR), which are directly involved in metabolic diseases like hypercholesterolemia, obesity and diabetes. Our goal is, through structural and biophysical studies, to identify molecules that selectively activate or represses these receptors. Also, for PPAR modulation, our research follows the new insight about PPAR phosporylation, discovered in 2009. This new approach postulates that is necessary to separate potency and agonism in PPAR case, in this way, the insulin sensitization is reached when the phosporylation is prevented.

Subprojects

Prospection of ligands for PPAR – undergraduate student.

Compounds identification for acting in diabetes control – undergraduate student.

Inhibition of PPAR phosporylation – research assistant CNPEM.

Regulation of gene transrepression and transactivation modulated by Nuclear Receptors.

The RNs are closely related to diseases like cancer, metabolic syndrome, diabetes, cardiopathies and obesity. They can act directly or indirectly in the regulation of transcription. In the direct regulation, RNs activate or represses the gene expression though their ligand modulation (transactivation). The indirect process occurs when RNs acts under other transcription factors (transrepression). Many studies have shown the direct participation of RNs in the transcription activation and repression. Others reported the influence of interaction of TFs and some nuclear receptors in diverse proteins expression regulation processes.

In this context, the importance of a better understanding about the interaction among RNs and other proteins, besides the mechanisms of transactivation and transrepression, is evident. Furthermore, this project purposes the study of interactions between RNs and DNA regulatory sequences (HREs); RNs and coregulators proteins; and RNs and transcription factors. The results will be used in order to seek more information about their action mechanisms, allowing that new regulation models of transcriptional regulation mediated by NRs could be purposed. Or even, that the already purposed models could be shown in a higher degree of details.

LNBio is part of the Brazilian Center for Research in Energy and Materials (CNPEM) - a private research and development institution (R&D) supervisioned by the Brazilian Ministry of Science, Technology, Innovation and Communication (MCTIC).